DESCRIPTION: (Applicant's Abstract) This project explores how drug craving is influenced by pharmacologic and associative factors, and develops a human laboratory model of associative drug craving. Drug craving is thought to be important in maintaining regular drug use in the current drug user and in leading to relapse in the former user. A complete understanding of drug craving and successful treatments that reduce drug craving are likely to involve both pharmacologic and associative factors. Pharmacologic factors that influence drug craving might be agonist or antagonist administration. Associative factors that influence drug craving might be stimuli that are related to drug delivery. This laboratory-based project uses cigarette smokers and cigarette craving to understand better how subjective craving and drug self-administration are influenced by agonist (nicotine) and antagonist (mecamylamine) administration, and by drug-related stimuli (e.g., smoke, cigarette, etc.). The project consists of four studies of cigarette smokers. The first study systematically examines the influence of nicotine and mecamylamine on subjective cigarette craving and on cigarette self-administration. The two medications will be presented alone and in combination, as recent data suggest that the combination may reduce craving more than either medication alone. The second study uses a Pavlovian extinction procedure to determine the associative nature of craving reductions elicited by denicotinized cigarettes. The study is based upon data from the animal laboratory demonstrating that extinction of the responses elicited by drug-related stimuli can require an extended period of unreinforced exposure. The third study examines the combined impact of pharmacologic and associative factors on cigarette craving. This study uses the most effective nicotine/mecamylamine combination from the first study to examine pharmacologic craving reduction while smokers smoke denicotinized or nicotinized cigarettes. The fourth study explores a human laboratory model of associative nicotine craving by pairing nicotine administration with environmental stimuli. In sum, this project examines how pharmacologic and associative factors influence subjective craving and drug self-administration using nicotine as a model drug, and cigarette smokers as model drug users. This rigorously designed project uses controlled, safe, and convenient laboratory methods, multidimensional measures, and powerful within-subjects designs. Data from this project will yield specific knowledge regarding cigarette craving and, more generally, will guide theoretical understanding of drug craving and influence medications development for drug abuse treatment.